Doi:10.1016/j.eururo.2011.08.055

a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m
Benign Prostatic Hyperplasia and Lower Urinary TractSymptoms: Research Priorities
Cosimo De Nunzio Sascha Ahyai , Riccardo Autorino Alexander Bachmann Waldemar Bialek Alberto Briganti , Oliver Reich Roman Sosnowski Nikesh Thiruchelvam Giacomo Novara
for the European Association of Urology Young Academic Urologists BPH Group
a Department of Urology, Sant’Andrea Hospital, University ‘‘La Sapienza,’’ Rome, Italy; b Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; c Urology Clinic, Second University of Naples, Naples, Italy; d Universita¨tsspital Basel, Urologische Klinik, Basel, Switzerland;e Department of Urology, University Hospital of Lublin, Lublin, Poland; f Department of Urology, Vita-Salute University San Raffaele, Milan, Italy;g Department of Urology, Munich-Harlaching Hospital, Munich, Germany; h Department of Urology, M. Sklodowska-Curie Memorial Cancer Center, Warsaw,Poland; i Department of Urology - Addenbrookes Hospital, Cambridge, UK; j Department of Oncological and Surgical Sciences, Urology Clinic, University of
Lower urinary tract symptoms (LUTS) and benign prostatic
safety issues and expert opinion, with a low level of evidence
hyperplasia (BPH) are highly prevalent in men beyond their
fourth decade . Previously, LUTS were thought to
Despite recent advances in the field, some issues related to
depend on BPH and bladder outlet obstruction (BOO) in men;
this condition are still under investigation. A number of
however, a simple cause-and-effect relationship cannot be
issues remain poorly understood in the field of BPH. The
established . In fact, benign prostatic enlargement (BPE)
pathophysiology of BPH remains a conundrum. Prostate
with LUTS remains a very common diagnosis in our daily
disorders occur as a result of aging, and the metabolic
practice. Epidemiologic studies suggest that age, genetic
changes associated with aging seem to be important. Despite
factors, and sexual hormones play major roles as risk factors
the current knowledge of risks factors, we do not know why
for BPH; the only known associations for BPH progression are
the prostate grows in one man and does not in others and
age and prostate volume More recently, metabolic
why symptoms develop in some and not in others
syndrome, detrusor overactivity, prostatic inflammation,
Aging is associated with an imbalance of sexual hormones,
cell-signaling disorders, and neurologic, cardiac, and renal
although the exact role in BPH initiation, development,
dysfunctions have been hypothesized to contribute to the
and progression remains obscure . Androgens have a
development of LUTS . Hence the very common urologic
permissive role in BPH, but there is no clear cause-and-effect
diagnosis of men with BPE and LUTS is likely to be
multifactorial and complex. Clinically, this is demonstrated
Nocturia still needs to be clarified. Storage symptoms are
by the fact that most patients with BPE suffer from LUTS, but
known to be most bothersome, and nighttime increased
only some patients presenting with LUTS have clinically
urinary frequency bothers not only patients but also their
partners. Research on nocturia treatment confirms that no
Revision of the terminology of LUTS became necessary to
therapy is truly effective, and surgery is not better than
reflect our understanding and to improve patient manage-
drugs in reducing the number of voids per night
ment. But validated instruments aimed at qualifying urinary
The importance of urodynamics in the assessment of
symptoms have not been implemented as widely as
patients with BPH is still under debate. For many years,
expected. Most recommendations for the use of diagnostic
clinical experience and dogma directed the management of
tests evaluating patients with LUTS continue to be based on
BPH and BOO, but only in the last decade did clinical
* Corresponding author. Department of Urology, Sant’Andrea Hospital, University ‘‘La Sapienza,’’ Rome, Italy. Tel. +39 0633777716.E-mail address: (C. De Nunzio).
0302-2838/$ – see back matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 1 2 0 5 – 1 2 0 6
research show that BOO is not necessarily a progressive
urologists with the purpose of boosting the research activity
condition and the outcome of BPH surgery may be
in some critical areas of urology and improving academic
independent of the degree of BOO. The question is not
collaboration among different centers in Europe. Specifically,
whether we need to do urodynamic evaluation in patients
we were given the task of investigation in the field of BPH and
with BPH but is the value of the information we obtain from
LUTS. We will start by looking at the feasibility of developing
pressure-flow studies Despite appropriate investigation
a BOO/BPH nomogram and improving diagnostic tools,
and surgical management, we continue to have patients who
characterizing BPH management in Europe, and determining
may remain symptomatic after prostatic surgery
the relationship between bladder stones and BPH. We hope
Urodynamic study is a powerful way to investigate
our energies will be enough to address some of the issues
bladder behavior in the storage phase and in the diagnosis
noted here. We find the task simultaneously daunting and
of obstruction, but the clinical value of bladder sensation and
detrusor dysfunction remains poorly understood One ofthe assumptions in this area is that symptoms in patients
Conﬂicts of interest: The authors have nothing to disclose.
with BPE are due to BOO, and treatment consists of reducingoutlet resistance to a minimum. However, the lowest class inthe Schaefer nomogram is not composed of normal
individuals but rather of patients who underwent trans-urethral resection of the prostate, suggesting this is a natural
[1] Briganti A, Capitanio U, Suardi N, et al. Benign prostatic hyperplasia
and its aetiologies. Eur Urol Suppl 2009;8:865–71.
nonobstructed condition . Finally, after 100 yr of BPH
[2] Alcaraz A, Hammerer P, Tubaro A, et al. Is there evidence of a
surgery, we do not know how much tissue we should remove.
relationship between benign prostatic hyperplasia and prostate
Adenomectomy removes the adenoma entirely, whereas
cancer? Findings of a literature review. Eur Urol 2009;55:864–75.
transurethral surgery leaves a variable degree of luminal
[3] Maserejian NN, Giovannucci EL, McKinlay JB. Dietary macronutri-
patency with no clear association with symptomatic control.
ents, cholesterol, and sodium and lower urinary tract symptoms in
Surgery is a difficult area of clinical research, and
surgeons sometimes avoid challenging successful proce-
[4] Abrams P, Grifﬁths D, Hofner K, et al. The urodynamics of LUTS. In:
dures and concepts of management with an evidence-based
Chatelain C, Denis L, Foo KT, et al. editors. Benign prostatic hyper-
view. Despite the fact that peer-reviewed literature
plasia. Plymouth, UK: Health Publications; 2001. p. 227–81.
flourishes, with hundreds of new papers published every
[5] Cabelin MA, Te AE, Kaplan SA. Benign prostatic hyperplasia: chal-
lenge in the new millennium. Curr Opin Urol 2000;10:301–6.
>300 papers were indexed in PubMed in 2010
[6] Cornu J-N, Cussenot O, Haab F, Lukacs B. A widespread population
dealing with these topics alone), several issues in the field of
study of actual medical management of lower urinary tract symp-
toms related to benign prostatic hyperplasia across Europe and
beyond ofﬁcial clinical guidelines. Eur Urol 2010;58:450–6.
The role of androgens and estrogens in LUTS due to BPH
[7] Helfand BT, Evans RM, McVary KT. A comparison of the frequencies of
medical therapies for overactive bladder in men and women: analysis
The prognostic value of BOO for BPH progression
of more than 7.2 million aging patients. Eur Urol 2010;57:586–91.
The prognostic value of detrusor underactivity and
[8] Porst H, McVary KT, Montorsi F, et al. Effects of once-daily tadalaﬁl
overactivity in the outcome of BPH treatment
on erectile function in men with erectile dysfunction and signs
The relationship between prostate debulking and out-
and symptoms of benign prostatic hyperplasia. Eur Urol 2009;
[9] Mamoulakis C, Ubbink DT, de la Rosette JJMCH. Bipolar versus
monopolar transurethral resection of the prostate: a systematic
Some of the relevant questions in medicine remain
review and meta-analysis of randomized controlled trials. Eur Urol
unanswered because, in the absence of an economic
interest, there is not enough drive to design, initiate, and
[10] Ahyai SA, Gilling P, Kaplan SA, et al. Meta-analysis of functional
complete the research needed to address the different
outcomes and complications following transurethral procedures
issues. The European Association of Urology has recently
for lower urinary tract symptoms resulting from benign prostatic
supported the development of groups of young academic
enlargement. Eur Urol 2010;58:384–97.

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